Spermidine is essential for fasting-mediated autophagy and longevity DOI Creative Commons
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1571 - 1584

Published: Aug. 8, 2024

Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers. Genetic pharmacological blockade endogenous synthesis fasting-induced nematodes cells. Furthermore, perturbing pathway vivo abrogated lifespan- healthspan-extending effects, as well cardioprotective anti-arthritic fasting. Mechanistically, mediated these effects via induction hypusination translation regulator eIF5A. In summary, polyamine–hypusination axis emerges a phylogenetically conserved metabolic control hub for fasting-mediated enhancement longevity.

Language: Английский

Cellular senescence and senolytics: the path to the clinic DOI Open Access
Selim Chaib, Tamar Tchkonia, James L. Kirkland

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 1556 - 1568

Published: Aug. 1, 2022

Language: Английский

Citations

650

The sirtuin family in health and disease DOI Creative Commons
Qi‐Jun Wu, Tie‐Ning Zhang, Huanhuan Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 29, 2022

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, involved numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles members SIRT family health disease conditions. Notably, this protein plays a variety important cellular biology such as inflammation, metabolism, oxidative stress, apoptosis, etc., thus, it is considered potential therapeutic target for different kinds pathologies including cancer, cardiovascular disease, respiratory other Moreover, identification modulators exploring functions these prompted increased efforts discover new small molecules, which can modify activity. Furthermore, several randomized controlled trials indicated that interventions might affect expression human samples, supplementation diverse impact on physiological function participants. In review, we introduce history structure family, discuss molecular mechanisms elaborate regulatory SIRTs summarize inhibitors activators, review related clinical studies.

Language: Английский

Citations

424

The landscape of aging DOI Open Access
Yusheng Cai, Wei Song, Jiaming Li

et al.

Science China Life Sciences, Journal Year: 2022, Volume and Issue: 65(12), P. 2354 - 2454

Published: Sept. 2, 2022

Language: Английский

Citations

244

Ageing and rejuvenation of tissue stem cells and their niches DOI
Anne Brunet, Margaret A. Goodell, Thomas A. Rando

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(1), P. 45 - 62

Published: July 20, 2022

Language: Английский

Citations

228

The ups and downs of caloric restriction and fasting: from molecular effects to clinical application DOI
Sebastian J. Hofer, Didac Carmona‐Gutiérrez,

Melanie I. Mueller

et al.

EMBO Molecular Medicine, Journal Year: 2021, Volume and Issue: 14(1)

Published: Nov. 15, 2021

Language: Английский

Citations

145

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice DOI
Heidi H. Pak, Spencer A. Haws, Cara L. Green

et al.

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(10), P. 1327 - 1341

Published: Oct. 18, 2021

Language: Английский

Citations

139

Mitochondria at the crossroads of health and disease DOI Creative Commons
Anu Suomalainen, Jodi Nunnari

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2601 - 2627

Published: May 1, 2024

Mitochondria reside at the crossroads of catabolic and anabolic metabolism—the essence life. How their structure function are dynamically tuned in response to tissue-specific needs for energy, growth repair, renewal is being increasingly understood. respond intrinsic extrinsic stresses can alter cell organismal by inducing metabolic signaling within cells distal tissues. Here, we review how centrality mitochondrial functions manifests health a broad spectrum diseases aging.

Language: Английский

Citations

122

Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain DOI Creative Commons

Matthew T. Buckley,

Eric Sun, Benson M. George

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 3(1), P. 121 - 137

Published: Dec. 19, 2022

Abstract The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop ‘aging clocks’ based on single-cell transcriptomics to characterize cell-type-specific rejuvenation. We generated transcriptomes from the subventricular zone neurogenic region 28 mice, tiling ages young old. trained single-cell-based regression models predict chronological age biological (neural stem proliferation capacity). These clocks are generalizable independent cohorts other regions brains, species. To determine if these could quantify transcriptomic rejuvenation, datasets two interventions—heterochronic parabiosis exercise. Aging revealed that heterochronic exercise reverse in regions, but different ways. This study represents first development high-resolution data demonstrates their application

Language: Английский

Citations

106

Dietary regulation in health and disease DOI Creative Commons
Qi Wu,

Zhijie Gao,

Xin Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Language: Английский

Citations

104

Mechanisms of spermidine-induced autophagy and geroprotection DOI Open Access
Sebastian J. Hofer, Anna Katharina Simon, Martina Bergmann

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 2(12), P. 1112 - 1129

Published: Dec. 22, 2022

Language: Английский

Citations

104